Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state
| Autor: | Emilie Besnard, Jean-Marc Lemaitre, Franck Pellestor, John De Vos, Sylvain Lehmann, Laure Lapasset, Jean-Marie Ramirez, Ollivier Milhavet, Nafissa Aït-Hamou, Alexandre Prieur, Amélie Babled, Julia Leschik |
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| Přispěvatelé: | Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cellular differentiation
Induced Pluripotent Stem Cells Mice SCID Biology Regenerative medicine Cell Line 03 medical and health sciences Research Communication Mice 0302 clinical medicine Mice Inbred NOD Genetics Animals Humans Rejuvenation Induced pluripotent stem cell ComputingMilieux_MISCELLANEOUS Cells Cultured Cellular Senescence 030304 developmental biology Aged Aged 80 and over 0303 health sciences [SDV.GEN]Life Sciences [q-bio]/Genetics Cell Differentiation Telomere Cellular Reprogramming Embryonic stem cell 3. Good health Cell biology Mitochondria Stem cell Cell aging Reprogramming 030217 neurology & neurosurgery Developmental Biology Transcription Factors |
| Zdroj: | Genes and Development Genes and Development, Cold Spring Harbor Laboratory Press, 2011, 25 (21), pp.2248-2253. ⟨10.1101/gad.173922.111⟩ |
| ISSN: | 0890-9369 |
| Popis: | Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which contributes to aging and restricted longevity, has been described as a barrier to the derivation of iPSCs. Here we demonstrate, using an optimized protocol, that cellular senescence is not a limit to reprogramming and that age-related cellular physiology is reversible. Thus, we show that our iPSCs generated from senescent and centenarian cells have reset telomere size, gene expression profiles, oxidative stress, and mitochondrial metabolism, and are indistinguishable from hESCs. Finally, we show that senescent and centenarian-derived pluripotent stem cells are able to redifferentiate into fully rejuvenated cells. These results provide new insights into iPSC technology and pave the way for regenerative medicine for aged patients. |
| Databáze: | OpenAIRE |
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